The overall objective of this "Research Center of Excellence in Pediatric Nephrology and Urology" is to provide a coordinated, interdisciplinary, and multi-institutional approach to study the development of the kidney during embryonic, fetal and postnatal life. The main theme of this Research Center is "Structural and Functional Development of the Kidney in Normal and Pathological Conditions". Broadly, the proposed research deals with fundamental questions of clinical relevance in Pediatric Nephrology such as the understanding of kidney morphogenesis and sodium homeostasis in health and disease. The experimental approaches range from examination of embryological, molecular and cellular biological mechanisms to integrative physiological studies of renal function during development. Project 1 will investigate the differentiation of the juxtaglomerular cell and its role in nephrovascular development. Project 2 will investigate the mechanisms regulating the development of the major proximal tubular transporting proteins (Na+/H+ exchanger, Cl-/base exchanger and Na+/K+ATPase) that regulate sodium excretion during fetal and postnatal life. Project 3 will determine the mechanisms that regulate the maturation of tubular surface membrane receptor - G protein/effector (transporter) coupling involved with sodium transport. Project 4 will examine how angiotensin regulates renal cellular phenotype, growth, and physiological responses to unilateral ureteral obstruction. The Research Center will be supported by two core facilities: administration and education. The accomplishments during the previous funding period provide assurance that this Research Center has the necessary manpower, focus, commitment, and institutional support to accomplish the proposed goals. It is anticipated that the Center of Excellence will build on the achievements of the past five years and will lead to improved management of infants and children with renal and urological diseases.